Community Acquired Pneumonia Challenges in the New Millenium DR. Yousef Noaimat MD.FCCP Consultant in pulmonary and internal medicine.

Community Acquired Pneumonia Definition: … an acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, accompanied by the presence of an acute infiltrate on a chest radiograph, or auscultatory findings consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for > 14 days before onset of symptoms. Adeel A. Butt, MD Bartlett. Clin Infect Dis 2000;31:

Community Acquired Pneumonia Epidemiology: 4-5 million cases annually ~500,000 hospitalizations ~45,000 deaths Mortality 2-30% <1% for those not requiring hospitalization Adeel A. Butt, MD Bartlett. CID 1998;26:

Epidemiology: (contd) fewest cases in yr group probably highest incidence in 65 yrs mortality disproportionately high in >65 yrs Community Acquired Pneumonia Adeel A. Butt, MD

Community Acquired Pneumonia Adeel A. Butt, MD # in 1000s Incidence

Community Acquired Pneumonia Adeel A. Butt, MD # in 1000s Mortality

Risk Factors for pneumonia age alcoholism smoking asthma immunosuppression institutionalization COPD PVD dementia Community Acquired Pneumonia Adeel A. Butt, MD ID Clinics 1998;12:723. Am J Med 1994;96:313

Risk Factors (contd.) Men: age and smoking, weight gain RR 1.5 for age 50-54, 4.17 for > 70 Smoking, current: RR 1.5; heavy: 2.54; Quit <10 yrs: 1.5 Weight gain >40 lbs since age 21 Women: smoking, BMI, weight gain BMI , RR 1.53: BMI >30, RR 2.22 Exercise protective: RR 0.66 for most active Alcohol consumption NOT associated with increased risk in men or women Community Acquired Pneumonia Adeel A. Butt, MD

Risk Factors in Patients Requiring Hospitalization older, unemployed, unmarried common cold in the previous year asthma, COPD; steroid or bronchodilator use Chronic disease amount of smoking alcohol NOT related to increased risk Community Acquired Pneumonia Adeel A. Butt, MD

Risk Factors for Mortality age bacteremia (for S. pneumoniae) extent of radiographic changes degree of immunosuppression amount of alcohol Community Acquired Pneumonia Adeel A. Butt, MD

S. pneumoniae: 20-60% H. influenzae: 3-10% Chlamydia pneumoniae: 4-6% Mycoplasma pneumonaie: 1-6% Adeel A. Butt, MD Community Acquired Pneumonia Legionella spp. 2-8% S. aureus: 3-5% Gram negative bacilli: 3-5% Viruses: 2-13% 40-60% - NO CAUSE IDENTIFIED 2-5% - TWO OR MORE CAUSES Microbiology

Community Acquired Pneumonia Adeel A. Butt, MD Evaluation for CAP

Laboratory Tests: CXR CBC with differential BUN/Cr glucose liver enzymes electrolytes Gram stain/culture of sputum pre-treatment blood cultures oxygen saturation Community Acquired Pneumonia Adeel A. Butt, MD

Diagnostic Evaluation CXR usually needed to establish diagnosis prognostic indicator rule out other disorders may help in etiological diagnosis Only 3% of outpatients and 28% of ER patients with suggestive signs and symptoms actually have pneumonia Adeel A. Butt, MD Community Acquired Pneumonia J Chr Dis 1984;37:215-25

Usefulness of Gram Stain Good sputum samples obtained from 39% 83% show one predominant morphotype Community Acquired Pneumonia Adeel A. Butt, MD

Community Acquired Pneumonia Adeel A. Butt, MD

PORT Publications: Class I: age < 50; 0/5 co-morbid conditions; normal or mildly deranged VS; normal mental status Class II-V: points assigned based on above, 5 co- morbid conditions, 5 PE findings, 7 lab or X-ray findings Community Acquired Pneumonia Adeel A. Butt, MD Fine MJ. NEJM 1997;336:243-50

Class I & II: usually do not require hospitalization Class III: may require brief hospitalization Class IV & V: usually do require hospitalization Community Acquired Pneumonia Adeel A. Butt, MD Fine MJ. NEJM 1997;336:243-50

Community Acquired Pneumonia Adeel A. Butt, MD

Severity of CAP RR > 30 PaO2/FiO2 < 250, or PO2 < 60 on room air Need for mechanical ventilation Mulitlobar involvement Hypotension Need for vasopressors Oliguria Altered mental status Adeel A. Butt, MD Community Acquired Pneumonia

Management Rational use of microbiology laboratory Pathogen directed antimicrobial therapy whenever possible Prompt initiation of therapy Decision to hospitalize based on prognostic criteria Adeel A. Butt, MD Community Acquired Pneumonia

Outpatient: macrolide doxycycline Fluoroquinolone NOT IN ANY SPECIFIC ORDER Adeel A. Butt, MD Community Acquired Pneumonia Empiric Treatment IDSA guidelines: Clin Infect Dis 2000;31:347-82

Patients in General Medical Ward: 3GC + macrolide B/B-I + macrolide OR B/B-I + FQ FQ alone Adeel A. Butt, MD Community Acquired Pneumonia Empiric Treatment IDSA guidelines: Clin Infect Dis 2000;31:347-82

Patients in ICU: 3GC + macrolide 3GC + FQ B/B-I + macrolide B/B-I + FQ Adeel A. Butt, MD Community Acquired Pneumonia Empiric Treatment IDSA guidelines: Clin Infect Dis 2000;31:347-82

Deviation From Guidelines Not many Studies done to assess this Prospective study in a tertiary care hospital Adherence to ATS guidelines was 88% No significant difference in mortality or LOS Mortality in Class V patients higher in nonadherent treatments Adherence to ATS associated with decreased mortality Mortality in Class I, II & III was ZERO. Menendez. Chest 2002;122:

Concerns about multiply resistant pneumococcus: 25-40% overall penicillin resistance intermediate resistance of questionable significance high level resistance associated with in vitro macrolide and 3GC resistance clinical failures not really documented Community Acquired Pneumonia Adeel A. Butt, MD IDSA guidelines: Clin Infect Dis 2000;31:347-82

Increased drug efflux coded by mefE susceptible to clindamycin most cases in US may be overcome by achievable levels of macrolides Community Acquired Pneumonia Adeel A. Butt, MD Ribosomal methylase coded by ermAM resistant to clindamycin mostly in Europe not overcome by standard doses Macrolide Resistance

Active against 98% of resistant pneumococcus Resistance has begun to increase Community Acquired Pneumonia Adeel A. Butt, MD (Newer)Fluoroquinolones Chen DK. NEJM 1999;341:233-9 Ho PL. Antimicrob Agents Chemother 1999;43: Wise R. Lancet 1996;348:1660

FQ Resistance 4 cases from Canada with pneumococcal pneumonia 1 died 2 developed resistance while on Rx 2 had resistant bugs to begin with Authors suggested that recent FQ use should be a contra-indication to using a FQ for empiric treatment of CAP Davidson. NEJM 2002;346:

FQ Resistance In a case control study, colonization or infection by FQ resistant pneumococci was independently associated with: COPD Nosocomial origin of bacteremia Residence in a nursing home Prior exposure to FQ Ho. Clin Infect Dis 2001;32:

Other Concerns Delay in diagnosis and treatment of TB Johns Hopkins study 33 patients with TB 16 received FQ for empiric Rx of CAP TB treatment initiation time: 21 days in the FQ group 5 days in the non-FQ group Dooley. Clin Infect Dis 2002;34:

Choice of Initial Antimicrobial Regimen Second generation generation cephalosporin plus a macrolide, non- pseudomonal third generation cephalosporin plus a macrolide, or a fluoroquinolone alone were all associated with a lower 30 day mortality in patients with CAP. Adeel A. Butt, MD Community Acquired Pneumonia Gleason. Arch Int Med 1999;159:

Macrolide Use and LOS: Patients who received macrolides within first 24 hours of admission had a shorter LOS (2.8 days vs. 5.3 days) Adeel A. Butt, MD Community Acquired Pneumonia Stahl. Arch Int Med 1999;159:

Azithromycin vs. Cefuroxime + Erythromycin prospective, randomized trial 145 patients Clinical cure 91% in each group. 4 S. pneumoniae strains with MIC ug/ml: 1/1 in azithromycin group cured, 2/3 in cef/erythro group cured Community Acquired Pneumonia Adeel A. Butt, MD Vergis. Arch Int Med 2000;160:

IV followed by Oral Azithromycin 615 patients: Azithromycin given to in a comparison trial with ATS recommended cefuroxime + erythromycin 77% vs 74% clinical cure or improvement Microbiological cure rates similar or better in azithromycin group Community Acquired Pneumonia Adeel A. Butt, MD

Cost-Effectiveness of IV-Oral Switch Therapy Azithromycin Mean cost - $4,104 CE Ratio per expected cure - $5,265 Cefuroxime + Erythro Mean cost - $4,578 CE Ratio per expected cure - $ 6,145 Paladino. Chest Oct 2002;122:

Clarithromycin ER Head-to-head comparison with FQ Vs. Levofloxacin patients Clinical cure 88% in Clarithro; 86% levo Radiographic success 95% vs. 88% Vs. Trovafloxacin 2 Clinical cure 87% vs. 95% Radiographic success 95% vs. 95%

Report from the DRSP Therapeutic Working Group Use a macrolide or doxycycline for outpatients Beta-lactam for inpatient Reserve FQ for: if above fails if allergic to any of the above documented high level resistance (pen MIC >4) Community Acquired Pneumonia Adeel A. Butt, MD

Summary We have some really good drugs available Use antibiotics judiciously Do consider local and national resistance patterns For Class I, II and possibly III, first line recommendations are a macrolide or doxycycline Revise therapy based on clinical and microbiological response Consider prior exposure when choosing an Abx